The findings, published online in the New England Journal of Medicine, showed the medicine combination led to an improvement in progression-free survival compared to exemestane alone. Progression-free survival is the length of time after study treatment begins that breast cancer does not grow.

Background and Reason for the Study

In postmenopausal women, standard treatment for hormone-receptor positive breast cancer is aromatase inhibitors,medicines that stop production of the estrogen that can stimulate growth of hormone-receptor positive cancer cells.

Not all cancers respond to aromatase inhibitors, and those that do may eventually become resistant to them. When cancer progresses the treatment options can include switching to a different aromatase inhibitor, or other medicines that block estrogen receptors.

Researchers are trying to identify new treatments that increase the effectiveness of hormonal therapies. They wanted to see if everolimus, which is approved by the U.S. Food and Drug Administration to treat advanced kidney cancer, could do this with certain locally advanced and metastatic breast cancers. Everolimus is in a family of medicines called mTOR inhibitors, which early studies suggest may complement estrogen-blocking medicines.

Structure of the Study

Researchers randomly assigned 724 women with hormone-receptor positive, HER2 negative locally advanced and metastatic breast cancer to two groups. The first group of 485 received exemestane and everolimus. The second group of 239 received exemestane and a placebo, or sugar pill. Participants, drawn from 189 cancer centers in 24 countries, had been previously treated with the hormonal therapy letrozole (Femara) or anastrazole (Arimidex), and the cancer had progressed.

The purpose of this study was to compare the two groups for progression-free survival. Researchers also looked at overall survival, the time from start of treatment until death from any cause, and response rate and side effects.

Results of the Study

Half the group that received exemestane and everolimus had no cancer growth for more than 7.2 months, while the other half had growth sooner. In the second group, half had no cancer growth for about 3.2 months, and the other half had growth sooner. These differences in progression-free survival were statistically significant, or unlikely to have happened by chance.

Response rate, the percentage of cancers that shrunk or disappeared after treatment, was 9.5 percent in the exemestane and everolimus group, and 0.4 percent in the group that received exemestane alone.

There were more side effects in the exemestane and everolimus group. These side effects, common with everolimus, included stomatitis, or inflammation in and around the mouth, fatigue, muscle weakness, diarrhea, fever and hyperglycemia, or high blood sugar.

The latest results from this study suggest the exemestane and everolimus group was twice as likely to show treatment benefit, compared to those who got exemestane alone. Researchers will continue to follow participants’ progress to see if overall survival also improved.

What This Means for You

If you’re being treated for metastatic breast cancer that has stopped responding to standard treatment, you and your care team are likely considering several options. Clinical trials may give you these, including treatment with medicines like everolimus not yet approved for use in breast cancer. If you have interest in a clinical trial, talk with your care team. You can also read LBBC’s Guide to Understanding Breast Cancer Treatment Research Studies for more information.